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Role of kainate/AMPA receptors in induction of striatal zif/268 and preprodynorphin mRNA by a single injection of amphetamine.

The role of kainate/AMPA excitatory amino acid receptors in D-amphetamine (AMPH)-induced behavioral changes and the induction of immediate early gene and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.), PPD mRNA and mRNA of the transcription factor zif/268, but not c-fos, was increased in dorsal striatum (caudate). Zif/268 mRNA was also increased in the sensorimotor cortex. Pretreatment of rats with DNQX, a kainate/AMPA receptor antagonist, did not affect the behaviors elicited by AMPH. However, the AMPH-stimulated increase in PPD and zif/268 mRNA levels in striatum, but not zif/268 mRNA in cortex, was blocked by DNQX pretreatment. In contrast, DNQX alone attenuated basal (constitutive) levels of zif/268 mRNA expression in sensorimotor cortical, but not in striatal, neurons. These studies indicate that kainate/AMPA receptors mediate the induction of zif/268 and PPD mRNA expression in the caudate nucleus induced by a single injection of AMPH. The fact that DNQX blocked genomic, but not behavioral, responses to acute AMPH suggests that kainate/AMPA receptor mechanisms may be involved in the long-term (possibly sensitizing) effects, rather than the acute effects, of the drug. In addition, tonic kainate/AMPA receptor stimulation may play a key role in maintaining constitutive expression of the zif/268 gene in cortical neurons.

Animals↗

Electrical sources in human somatosensory cortex: identification by combined magnetic and potential recordings.

Magnetic fields and electrical potentials produced by neuronal activity have different properties that can be used for the identification of electrical sources in the human brain. Fields and potentials occurring 20 to 30 milliseconds after median nerve stimulation in human subjects were compared in order to investigate the sources of evoked potential components that have been attributed by different investigators to the thalamus or thalamocortical afferents, to separate radial sources in somatosensory cortex and motor cortex, or to a tangential source in somatosensory cortex. The magnetic and potential wave forms were highly similar in morphology, and their spatial distributions were centered over sensorimotor cortex, were dipolar in shape, and differed in orientation by approximately 90 degrees; distances between the minimum and maximum of the magnetic distributions were about 60 percent of those of the potential distributions. These results cannot be accounted for by thalamic sources or radial cortical sources alone, but are consistent with a tangential source in somatosensory cortex, with an additional smaller contribution from radial sources.

Electrophysiology↗

Clinical deterioration in probable Alzheimer's disease correlates with progressive metabolic impairment of association areas.

Regional cerebral glucose metabolism (rCMRG1) measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose was studied longitudinally (interval ranging from 6 to 27 months) in 25 patients with probable Alzheimer's disease (AD). A significant decline of rCMRG1 was noted in the whole brain (p = 0.02) which was most pronounced in the temporoparietal (p = 0.002), frontal (p = 0.01), superior parietal (p = 0.01) and occipital (p = 0.03) association cortex. A similar decline was also present in the thalamus (p = 0.04) but not in the primary visual and sensorimotor cortex, basal ganglia, cerebellum and brainstem. The changes of rCMRG1 in the temporoparietal, frontal and occipital association cortex were related to the change of the Mini Mental State Examination score (temporoparietal: r = 0.49, p = 0.01; frontal: r = 0.40, p = 0.05; occipital: r = 0.44, p = 0.03). The rate of clinical and metabolic decline was not related to age at onset, sex, family history or duration of disease. The results suggest that clinical deterioration and metabolic impairment in probable AD are closely related and dependent on progression of pathological changes in cortical association areas.

Aged↗

[Anticonvulsive effect of superoxide dismutase].

The influence of superoxide dismutase (SOD) on the development of focal epileptic activity (EpA) in the rat brain cortex has been investigated. Intraperitoneal administration of SOD to rats (1 mg/kg) 30 minutes before penicillin application to the sensorimotor cortex led to marked relaxation of EpA and a decrease in the concentration of lipid peroxidation (LPO) products in EpA focus. The results corroborate our earlier assumption on an important pathogenetic role of LPO disturbances in epileptogenesis and make reasonable the combination of the traditional anticonvulsive therapy with the agents activating the oxidative system.

Animals↗

Synaptic organization and prefrontal corticothalamic termination in the mediodorsal thalamic nucleus of the cat.

The synaptic organization of the mediodorsal thalamic nucleus (MD) in the cat have been studied with the electron microscope, and correlated with the termination of the medial prefrontal corticothalamic afferents using the method of anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The neuropil of MD was divided into glomerular and extraglomerular regions. A synaptic glomerulus was composed of a central dendrite and some different presynaptic profiles with astroglial ensheathment. The prevalent presynaptic elements in glomeruli were presynaptic dendrites (PSDs) that contained pleomorphic vesicles, and formed symmetric synaptic contacts and puncta adhaerentia junctions with central dendrites. One or two large terminals with round vesicles and asymmetric specializations (LR) also participated in glomerular formations. They were invariably presynaptic to central dendrites and PSDs. As terminals less frequently found within glomeruli, there were small-sized terminals with round vesicles and asymmetric synaptic junctions with PSDs. In the extraglomerular neurophils, small to medium-sized terminals with pleomorphic vesicles (SMP) were found besides the presynaptic profiles identified in glomerular regions. These SMP terminals formed axodendritic and axosomatic symmetric synapses. WGA-HRP injections into the medial prefrontal cortex resulted in anterograde labelings in not only SR but also LR presynaptic terminals. SR boutons made up the majority of labeled terminals, and they were found only in the extraglomerular neuropil. While labeled LR terminals were detected in the extraglomerular neuropil and synaptic glomeruli with less encounter. The results of the present study show that the synaptic organization in MD of the cat is similar to that in other thalamic relay nuclei and in MD of the monkey. Further, MD receiving two subsets of synaptic terminations from the prefrontal cortex might play a different functional role in regulating the neural circuit between MD and the prefrontal cortex in comparison with that in the sensory and motor thalamic nuclei that receive only SR terminals from the sensorimotor cortex.

Animals↗

Safe surgery of lesions near the motor cortex using intra-operative mapping techniques: a report on 50 patients.

In 50 patients lesions located in or adjacent to the motor strip were microsurgically removed with the help of intra-operative electrophysiological mapping of the sensorimotor cortex. Mapping consisted of cortical stimulation and/or recording of somatosensory evoked potentials. Depending on the patient's pre-operative neurological status, surprisingly good results could be achieved: The surgery resulted in increased permanent sensorimotor deficit in only 4% of cases and in improved neurological status in 30% of cases. It is concluded that surgical removal of centrally located lesions using a microsurgical technique and intra-operative mapping of the motor cortex is safe and permits extensive or radical resection of lesions, even those in the motor cortex itself.

Adult↗

Biphasic effects of polarizing current on adenosine-sensitive generation of cyclic AMP in rat cerebral cortex.

Cyclic AMP accumulation elicited by adenosine was investigated in cortical slices of rats following the application of a weak anodal direct current (anodal polarization) to the unilateral sensorimotor cortex. Anodal polarization with 3.0 microA for 30 min caused an increase in the adenosine-elicited accumulation of cyclic AMP in the polarized cortex, in which case the increase in the polarized cortical region was highlighted by repeated applications of the currents. Polarization with 0.3 microA for 30 min decreased the cyclic AMP accumulation, and polarization with 30.0 microA for 30 min had no effect. When applied for 3 h, the polarizing currents at all of the intensities tested decreased the cyclic AMP accumulation. The results indicate that anodal polarization has biphasic effects on adenosine-elicited accumulation of cyclic AMP in the cortex. Alterations in the cyclic AMP generation are suggested to form the neurochemical basis of central and behavioral activity induced by anodal polarization.

Adenosine↗

Contrasting EEG profiles elicited by antipsychotic agents in the prefrontal cortex of the conscious rat: antagonism of the effects of clozapine by modafinil.

1. Power spectra (0-30 Hz) were recorded from transcortical electrodes implanted in prefrontal and sensorimotor cortex in conscious rats. For each animal, the spectra in the presence of a drug were divided by the spectra in the presence of vehicle to give a drug-related differential display of the power spectra, the profile of EEG effects. 2. The profiles of a range of antipsychotic agents of different classes were compared. Haloperidol (0.5 mg kg-1 and 1 mg kg-1 s.c., peak 8 - 12 Hz), chlorpromazine (0.5 mg kg-1, i. p., peak 8 Hz), levomepromazine (1 mg kg-1, i.p., peak 8 Hz), quetiapine (2.5 mg kg-1, s.c., peak 9 - 12 Hz), sertindole (2.5 mg kg-1, s.c., peak 6 - 14 Hz), risperidone (0.5 and 1 mg kg-1 i.p., peak 9 Hz), clozapine (0.1, 0.2, 0.3 and 5 mg kg-1, s.c., peak 8 Hz) and MDL100907 (0.01 mg kg-1 s.c. peak 2 Hz) synchronized the EEG, increasing the power spectra between 2 and 30 Hz, although there were marked differences between the individual profile of EEG effects for each drug. 3. In contrast, the benzamides, sulpiride (7.5 and 15 mg kg-1 i.p.), and amisulpiride (1 and 15 mg kg-1 i.p.) caused marked asynchronous changes in the EEG. Raclopride (2.5 mg kg-1 i.p.), caused an initial peak at 9 Hz, but the effects of raclopride desynchronized over a 3 h time period. 4 Modafinil and apomorphine, administered alone, decreased the power spectra at frequencies higher than 4. Hz. Modafinil (62.4 mg kg-1, i.p.) selectively antagonized the effects of clozapine, but did not antagonize the effects of raclopride. 5. Different pharmacological classes of antipsychotic show synchronization or desynchronization of the EEG in the prefrontal cortex, with the benzamides showing a distinctive spectrum. There appears to be a specific interaction between modafinil and clozapine. Thus, modulation of prefrontal cortical function, perhaps by thalamic gating, may be important for antipsychotic activity.

Animals↗

[Establishment of interhemispheric asymmetry of transcallosal potentials in the sensomotor cortex of cats].

In acute experiments on 1 to 21-day old kittens immobilized with diplacin, a study was made of asymmetry of transcallosal responses (TCR) in the sensorimotor cortex. Interhemispheric asymmetry was detected by the positive and negative phases of the responses which was of an individual nature. In the course of development, the asymmetry of the TCR positive component virtually remained unchanged, while that of the negative component increased in size and incidence. Basic types of interhemispheric responses asymmetry were defined (qualitative, quantitative, topographic and quantitative-topographic) and its properties were established; partiality of dominance, callosal nature and dynamics. The interrelation of both TCR components was shown in the formation of the asymmetry and two its forms were revealed: synchronous and asynchronous.

Animals↗

"Willed action": a functional MRI study of the human prefrontal cortex during a sensorimotor task.

Functional MRI (fMRI) was used to examine human brain activity within the dorsolateral prefrontal cortex during a sensorimotor task that had been proposed to require selection between several responses, a cognitive concept termed "willed action" in a positron emission tomography (PET) study by Frith et al. [Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. (1991) Proc. R. Soc. London Ser. B 244, 241-246]. We repeated their sensorimotor task, in which the subject chooses to move either of two fingers after a stimulus, by fMRI experiments in a 2.1-T imaging spectrometer. Echo-planar images were acquired from four coronal slices in the prefrontal cortex from nine healthy subjects. Slices were 5 mm thick, centers separated by 7 mm, with nominal in-plane spatial resolution of 9.6 x 5.0 mm2 for mean data. Our mean results are in agreement with the PET results in that we saw similar bilateral activations. The present results are compared with our previously published fMRI study of a verbal fluency task, which had also been proposed by Frith et al. to elicit a "willed action" response. We find a clear separation of activation foci in the left dorsolateral prefrontal cortex for the sensorimotor (Brodmann area 46) and verbal fluency (Brodmann area 45) tasks. Hence, assigning a particular activated region to "willed action" is not supported by the fMRI data when examined closely because identical regions are not activated with different modalities. Similar modality linked activations can be observed in the original PET study but the greater resolution of the fMRI data makes the modality linkages more definite.

Female↗

Language activation studies with positron emission tomography.

Behavioural tasks produce changes in regional cerebral blood flow (rCBF), the result of increased local neural activity. These changes can be measured with positron emission tomography (PET). Language activation studies by means of PET are being used to relate regional patterns of cerebral activation to information-processing models of speech and reading. Significant activation confined to both superior temporal gyri has been observed when normal subjects hear words played backwards, listen to non-words, and perform category judgements on pairs of heard real words. Prestriate cortex is activated by seeing strings of letter-like symbols, consonant strings, pronounceable non-words and real words, with additional activation in left medial prestriate cortex in response to the non-words and real words. Left posterior superior temporal gyrus (PSTG), left dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA) are engaged when subjects retrieve verbs from memory to match nouns. Finally, primary sensorimotor cortex is activated during articulation. There is particular interest at present in the precise roles of left PSTG and DLPFC in single-word comprehension and generation, and interpretation of the results depends critically on the design of the single-word tasks used for behavioural activation.

Aphasia↗

Cortico-muscular coupling in a patient with postural myoclonus.

We investigated the cortico-muscular coherence in a patient with posturally induced cortically originating negative myoclonus. We recorded simultaneously 50 channels EEG and EMG from quadriceps and biceps femoris muscles of the left upper leg. Three experimental conditions were investigated with the patient in a seated position: (i) recording during rest (Rest), (ii) recording while the patient had to hold his left leg horizontally stretched out (Postural), and (iii) recording while the patient had to hold his left leg horizontally stretched out against a vertical force (Postural against force). Coherence, phase difference and cumulant density were computed as indicators for cortico-muscular coupling. The cortical component preceding the silent period was shown by averaging and was reconstructed. During postural and postural against force conditions, the EEG over the vertex was significantly coherent with EMG, in alpha (7-15 Hz) and beta range (15-30 Hz). The strongest coherence peak was at 21 Hz. No high-frequency coherence was observed. The phase difference and the cumulant density estimate corresponded to a 32 ms time lag between motor cortex and muscles, with EEG leading. The broadening of the coherence spectrum at which the motor cortex drives the muscles together with the excessive coherence levels and the giant SEP could reflect the hyperexcitability of the sensorimotor cortex. The frequency content of the coherence may be characteristic for this type of myoclonus. The results lend support to the view that the frequency analysis may have some diagnostic potential in cortical myoclonus.

Aged↗

[Changes in the structural and functional states of chromatin of the neurons of the cerebral hemisphere cortex in the early post-resuscitation period in rats].

Structuro-functional state of chromatin of the neurons' nuclei of the third, fourth and fifth layers of the sensorimotor cortex was investigated by Moore's method and with the help of ammonia silver colouring an hour and 24 hr post resuscitation in rats who had endured a systemic arrest of blood circulation. It was determined, that the level of labelling of nucleoli of light neurons increased in the early postresuscitation period, while that of dark neurons decreased as compared to check samples. The level of labelling of extranucleolar chromatin increased in both light and dark neurons in the cortex layers under investigation during the 1st hour post resuscitation. The transcriptional activity of extranucleolar chromatin of neurons of both types remained increased in the third and fourth cortex layers 24 hr post resuscitation, while in the fifth one it tended to normalize during the same period. Essential restructuring of the neurons's chromatin was determined with the help of ammonia silver in all cortex layers, which was indicative of a possible change in the spectrum of the synthesized proteins.

Animals↗

A functional neuroanatomy of tics in Tourette syndrome.

BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors often associated with irresistible urges. They are a defining symptom of the classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an example of disordered human volition. The neural correlates of tics are not well understood and have not been imaged selectively. METHODS: Event-related [(15)O]H(2)O positron emission tomography techniques combined with time-synchronized audio and videotaping were used to determine the duration of, frequency of, and radiotracer input during tics in each of 72 scans from 6 patients with TS. This permitted a voxel-by-voxel correlational analysis within Statistical Parametric Mapping of patterns of neural activity associated with the tics. RESULTS: Brain regions in which activity was significantly correlated with tic occurrence in the group included medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, the Broca's area, superior temporal gyrus, insula, and claustrum. In an individual patient with prominent coprolalia, such vocal tics were associated with activity in prerolandic and postrolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in sensorimotor cortex was noted with motor tics. CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits identified in this study may account for the initiation and execution of diverse motor and vocal behaviors that characterize tics in TS, as well as for the urges that often accompany them. Arch Gen Psychiatry. 2000;57:741-748

Adult↗

Behavioral recovery and anatomical plasticity in adult rats after cortical lesion and treatment with monoclonal antibody IN-1.

We have previously reported that monoclonal antibody (mAb) IN-1 treatment after ischemic infarct in adult rats results in significant recovery of skilled forelimb use. Such recovery was correlated with axonal outgrowth from the intact, opposite motor cortex into deafferented subcortical motor areas. In the present study, we investigated the effects of mAb IN-1 treatment after adult sensorimotor cortex (SMC) aspiration lesion on behavioral recovery and neuroanatomical plasticity in the corticospinal tract. Adult rats underwent unilateral SMC aspiration lesion and treatment with either mAb IN-1 or a control Ab, or no treatment. Animals were then tested over a 6-week period in the skilled forelimb use task and the skilled ladder rung walking task. We found that animals treated with mAb IN-1 after SMC lesion fully recovered the use of forelimb reaching, but showed no improvement in digit grasping as tested in the skilled forelimb use task. The mAb IN-1 treatment group was also significantly improved as compared to control groups in the skilled ladder rung walking test. Furthermore, neuroanatomical tracing revealed a significant increase in the corticospinal projections into the deafferented motor areas of the spinal cord after mAb IN-1 treatment. These results indicate that treatment with mAb IN-1 after cortical aspiration lesion induces remodeling of motor pathways resulting in recovery in only certain behavioral tasks, suggesting that the cause of brain damage influences behavioral recovery after mAb IN-1 treatment.

Analysis of Variance↗

Temporal modulation of GABA(A) receptor subunit gene expression in developing monkey cerebral cortex.

In situ hybridization histochemistry was used to examine the expression of 10 GABA(A) receptor messenger RNAs corresponding to the alpha1-alpha5, beta1-beta3, gamma1 and gamma2 subunits in primary somatosensory and visual areas of macaque monkey cerebral cortex from embryonic day (E) 125 to postnatal day (P) 125. Results were compared with expression patterns in adults. In the sensorimotor cortex at E125, overall levels of all subunit transcripts were low. At E137, there was a major lamina-specific increase in all subunit messenger RNAs except gamma1. For alpha1, alpha2, alpha4, beta2, beta3 and gamma2 subunit transcripts, this increase was highest in areas 3a and 3b, particularly in layers III/IV and VI. Postnatally, there were significant decreases in all transcripts. Alpha1, alpha5, beta2 and gamma2 subunit transcripts, while still at significantly lower levels than at E137, remained expressed at levels higher than other transcripts. Unlike in rodents, there was no obvious "switch" in the major subunits expressed in fetal and adult cortex, alpha1, alpha5, beta2 and gamma2 remaining highest throughout. In area 17, the most prominently expressed subunits at earliest ages were alpha2, alpha5, beta1, beta2, beta3 and gamma2, especially in layers II/III and VI. At E150, expression for alpha2, alpha3, beta1 and beta3 subunit transcripts in these layers decreased, but levels for alpha1, alpha4, alpha5, beta2, gamma1 and gamma2 transcripts increased, particularly within layer IV. The increase at E150 was particularly marked for alpha5 transcripts, which were expressed at levels more than four times those of other transcripts. Alpha1, beta2 and gamma2 remain highest into aduthood. Fetal area 17 displayed lamina-specific patterns of expression not found in adult animals. In particular, alpha3 messenger RNAs were present in layer IVA and gamma1 transcripts were present in layer IVC at E150, despite a lack of expression in these layers in the adult. These data demonstrate increased expression of GABA(A) receptors during the period of establishment of thalamocortical and intracortical connections, and a temporal regulation that may be associated with the period of developmental plasticity.

Aging↗

Norepinephrine-elicited accumulation of cyclic AMP in slices of rat cerebral cortex polarized with a weak anodal current.

Cyclic AMP accumulation in response to norepinephrine was examined in slices of rat cerebral cortex the day after a unilateral application of anodal current of 0.3, 3.0 or 30 microA to the surface of the sensorimotor cortex. When 3.0 microA was applied, the norepinephrine-elicited accumulation of cyclic AMP was greater in the cortical area including the application point than in either the contralateral cortical area or non-polarized control cortical slices. The changes in cyclic AMP accumulation are discussed in relation to the role of the direct current in producing functional changes in the cortex.

Animals↗

[Modulation of pyramidal responses of the sensomotor cortex after combined stimulation of the lateral hypothalamus and the sensomotor cortex of the rat].

Periodical pyramidal tract (PT) stimulation in freely moving rats has been shown to be accompanied by statistically significant increased functional activity of neuronal populations of the sensorimotor cortex (SMC) manifesting as potentiation of the primary positive phase of the pyramidal-cortical response (PCR). When periodical PT stimulation is combined with the lateral hypothalamus (LH) stimulation of the same periodicity, a statistically significant increase in the magnitude of potentiation of the PCR positive phase compared to that occurring without the LH activation is observed. When the periodical PT stimulation is combined with the LH and SMC stimulation of the same periodicity, the potentiation of the PSR positive phase increases significantly in comparison with the potentiation occurring without the SMC stimulation.

Animals↗